Abstract
BackgroundPyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence.MethodsThe objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial.Trial registrationCurrent controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.
Highlights
Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration
The decision to power the STOP GAP trial on the basis of superiority was made as (i) ciclosporin is considerably more expensive than prednisolone; (ii) case series and clinical experience give the impression that ciclosporin may gain control more quickly, and have a side-effect profile that is more suitable for long-term therapy; and (iii) pragmatically, for a rare condition such as PG, this was felt to be the best approach as an equivalence trial would require a much larger trial that could only be delivered internationally, which was beyond the scope of our funding
The STOP GAP trial is a unique study that could not be achieved without the collaborative efforts of large numbers of participating dermatologists, nurses, NHS Trusts and research networks
Summary
Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. Pyoderma gangrenosum (PG) is a rare inflammatory dermatosis characterised by painful and rapidly progressive skin ulceration [1,2] It most commonly affects the lower limbs, but can affect any other site including the peristomal area. Other reviews have suggested a similar stepwise approach [7] These recommendations were based on case series alone as no RCTs of these most commonly used treatments were identified and clinical guidelines are currently lacking. These treatments are currently being used for patients with PG without rigorous testing, or understanding of their relative efficacy, cost and side-effect profile
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